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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Other Sizes |
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Purity: ≥98%
GSKJ1 (GSK-J1; GSK-J 1; GSK-J-1) is a novel, highly selective and potent inhibitor of histone demethylase (H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A) with potential antineoplastic activity. It that has significant activity (IC50 60 nM for human JmjD3) in vitro and in cell assays using an ester prodrug derivative (GSK-J4: 1 µM < IC50 < 10 µM; e.g. 9 µM in primary human macrophages). The methyl groups from tri- and dimethylated lysine 4 of histone H3 are removed by the KDM5/JARID1 family of Fe(II)- and α-ketoglutarate-dependent demethylases. KDM5A (JARID1A/RBP2) and KDM5B (JARID1B/PLU1) may play a role as oncogenic drivers, according to mounting evidence from primary tumors and model systems. As an ester derivative (GSK-J5) in cells and a control for target effects in vitro, the pyridine regioisomer GSK-J2 exhibits significantly less on-target activity (IC50 > 100 µM for human JmjD3). Recent data against H3K4me3/2/1 demethylases indicates that GSK-J1 also exhibits some activity (IC50 950 nM for Jarid1b, IC50 1.76 uM for Jarid1c).
Targets |
JMJD3 ( IC50 = 60 nM )
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ln Vitro |
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ln Vivo |
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Enzyme Assay |
Purified JmjD3 (1 μM) and UTX (3 μM) are incubated with a 10 μM peptide [Biotin-KAPRKQLATKAARK(me3)SAPATGG]. in 50 mM HEPES pH 7.5, 150 mM KCl, 50μM (NH4)2SO4·FeSO4·H2O, 1 mM 2-oxoglutarate, and 2 mM ascorbate (JmjD3, 3 minutes at 25°C; UTX, 20 minutes at 25°C) had different inhibitor concentrations (0, 0.005, 0.01, 0.02, 0.05, 0.1 μM). To halt the reaction, add 10 mM EDTA. Utilizing a zip tip to desalt the reaction, the reaction is then spotted using an α-cyano-4-hydroxycinnamic acid MALDI matrix on a MALDI plate. Via the MALDI-TOF R system, samples are analyzed.
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Animal Protocol |
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References |
Molecular Formula |
C22H23N5O2
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Molecular Weight |
389.45
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Exact Mass |
389.19
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Elemental Analysis |
C, 67.85; H, 5.95; N, 17.98; O, 8.22
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CAS # |
1373422-53-7
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Appearance |
Solid powder
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SMILES |
C1CN(CCC2=CC=CC=C21)C3=NC(=NC(=C3)NCCC(=O)O)C4=CC=CC=N4
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InChi Key |
AVZCPICCWKMZDT-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C22H23N5O2/c28-21(29)8-12-24-19-15-20(26-22(25-19)18-7-3-4-11-23-18)27-13-9-16-5-1-2-6-17(16)10-14-27/h1-7,11,15H,8-10,12-14H2,(H,28,29)(H,24,25,26)
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Chemical Name |
3-[[2-pyridin-2-yl-6-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidin-4-yl]amino]propanoic acid
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.5677 mL | 12.8386 mL | 25.6772 mL | |
5 mM | 0.5135 mL | 2.5677 mL | 5.1354 mL | |
10 mM | 0.2568 mL | 1.2839 mL | 2.5677 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Structure of the inhibitor GSK-J1 bound in the catalytic pocket of human JMJD3. Nature . 2012 Aug 16;488(7411):404-8 td> |
GSK-J1 is selective for H3K27 demethylases of the KDM6 subfamily and specifically binds to endogenous JMJD3. Nature . 2012 Aug 16;488(7411):404-8. td> |
GSK-J1 inhibits TNF-α production by human primary macrophages in an H3K27-dependent manner. Nature . 2012 Aug 16;488(7411):404-8. td> |
J Biol Chem . 2022 Jun;298(6):102017. td> |